Pathophysiology Chapter 4

Cellular Adaptation

Reversible response to physiologic (normal) and pathologic (adverse) changes. Adaptations to pathological conditions are usually only temporarily successful. Prolonged or severe pathological conditions will ultimately lead to cell death.

Adaptive changes: Atrophy, Hypertrophy, Hyperplasia, Dysplasia, Metaplasia

Atrophy

Decrease in cellular size. Decreases organ size if enough cells shrink.

Physiologic: Normal in aging

E.g. thymus shrinking during early childhood development

Pathologic: Results from decreases in workload, pressure, use, blood supply, nutrition, hormonal/neural stimulation

E.g. limb in a cast, prolonged bed rest/ immobilization

Hypertrophy

Increase in cellular size. Increases organ size

Physiologic:

Results from increased demand, stimulation by hormones, growth factors

E.g. exercise or weightlifting, pregnant uterus

Pathologic:

Results from chronic hemodynamic overload in HF

Hyperplasia

Increase in number of cells. Increased rate of cellular division

Physiologic:

Compensatory—enables organs to regenerate

Hormonal—in organs that respond to endocrine hormonal control

Pathologic:

Abnormal proliferation of normal cells d/t hormonal stimulation

BPH, uterine endometrium

Dysplasia

Deranged cellular growth. Abnormal changes in size, shape, organization of mature cells. May be reversible if triggering stimulus is removed. Tissue appears disorderly, but is not cancer. Low grade vs. high grade. If changes penetrate basement membrane: invasive neoplasm

Metaplasia

Replacement of one type of cell with another.Reversible replacement of one mature cell type by another. Associated with tissue damage, repair, regeneration. Reprogramming of stem cells or undifferentiated mesenchymal cells

Cellular Injury

Occurs if cell unable to maintain homeostasis

Reversible? Cells recover

Irreversible? Cells die

Hypoxic injury

Single most common cause of cellular injury.

Results from:

Ischemia—reduced supply of blood

Reduced oxygen content in ambient air

Loss of hemoglobin

Decreased production of red blood cells

Diseases of the respiratory and cardiovascular systems

Poisoning of the oxidative enzymes (cytochromes) within the cells

Anoxia—total lack of oxygen caused by obstruction

MI

Ischemia-reperfusion injury (lack of blood + restoring blood flow)

Cell injury and death caused by restoration of blood flow and oxygen

Mechanisms:

Oxidative stress

Increased intracellular calcium concentration

Inflammation

Complement activation

Free radicals and reactive oxygen species

Cause oxidative stress

Free radical is electrically uncharged atom or group of atoms with an unpaired electron that damage:

Lipid peroxidation

Protein alteration

DNA damage

Mitochondrial effects

Chemical & Toxic Injury

Xenobiotics—toxic, mutagenic, carcinogenic: Carbon tetrachloride, Lead, Carbon monoxide, Ethanol, Mercury, Social or street drugs, Opioid abuse, Over-the-counter and prescribed drugs, Air pollution

Leading cause of child poisoning is medications

E.g. Acetaminophen

Unintentional and Intentional Injuries

More common among men and higher rates among blacks. Blunt force injuries result of application of mechanical force to body. Results in tearing, shearing, or crushing of tissues. ex. Motor vehicle accidents and falls, Contusions, Lacerations, Fractures. Sharp force injuries: Incised wound, Stab wound, Puncture wound, Chopping wound. Gunshot wounds. Asphyxial injuries caused by a failure of cells to receive or use oxygen: Suffocation, Choking asphyxiation, Strangulation, Hanging, ligature, and manual strangulation. Chemical asphyxiants: Carbon monoxide, cyanide, and hydrogen sulfide, Drowning

Infectious Injury

Pathogenicity of a microorganism Disease-producing potential: Invasion and destruction, Toxin production, Production of hypersensitivity reactions

Immunologic and Inflammatory Injury

Injury from substances generated during inflammatory response: Phagocytes, Biochemical substances, Histamine, antibodies, lymphokines, complement system products, and proteases. Membrane alterations leading to infiltration, Excess water, proteins, lipids & carbohydrates, Endogenous substances & exogenous substances

Accumulations result from four mechanisms

Insufficient removal of normal substance because of altered transport, Accumulation of abnormal substance because of defects, Inadequate metabolism of endogenous substance because of lack of lysosomal enzyme, Harmful exogenous materials

Systemic Manifestations of Cell Injury

Fever, Increased heart rate, Increase WBC, Pain, Elevated liver enzymes

Necrosis

Outside of cell. Cell injury → death. Inflammatory response. Cell death characterized by swelling of cell organelles, rupture of the plasma membrane, spillage of intracellular contents into surrounding tissue → tissue damage. Causes of necrosis: Ischemia, Microbial toxins, Chemical/ physical injury

Apoptosis

Inside the cell. Programmed cell death. normal part of aging

Autolysis (autodigestion)

Cells self- digest

Coagulative necrosis

infarct

Liquefactive necrosis

Neurons and glial cells of the brain. Hydrolytic enzymes. Bacterial infection: Staphylococci, Streptococci, and Escherichia coli

Caseous necrosis

Cheese like appearance. Tuberculous pulmonary infection. Combination of coagulative and liquefactive necrosis.

Fat necrosis (death of fat cells)

Breast, pancreas, and other abdominal organs. Action of lipases. Lipases break down triglycerides in fat cells → releases free fatty acids. Free fatty acids combine with calcium forming the appearance of “opaque, chalky deposits)– fat saponification

Gangrenous necrosis

Death of tissue from severe hypoxic injury. Dry vs. wet gangrene. Gas gangrene: Clostridium, Deep puncture wounds from soil-contaminated objects. Deadly - leads to shock

Physiologic

a normal programmed cell death to maintain health & homeostasis (e.g. aging RBC)

Pathologic

excessive or inappropriate apoptosis that occurs because of a disease (e.g. chemo: cancer + healthy cells)

Autophagy

Self-destructive and a survival mechanism where a cell degrades & recycles its own components through lysosomes. Cytoplasmic contents delivered to lysosomes for degradation. Purpose is survival: conserve energy, remove damaged organelles, adaptation to stress. Contributes to the aging process.

Frailty

Weakness, decreased stamina, and functional decline in older adults. Increases vulnerability to falls, disability, disease, death

Somatic Death

Death of entire body. Postmortem changes are diffuse. ends with decomposition and skeletonization

Pallor mortis

skin becomes pale and yellowish

Algor mortis

decrease in body temperature

Rigor mortis

stiffness of the muscles (within 6 hrs)

Livor mortis

blue-purple discoloration of the skin over dependent tissues

Putrefaction

tissues & organs break down (24-48hrs)